The research focuses on orexins, the small, specialized fraction of the brain’s 100 billion neurons that play a key role in regulating the body’s wakeful state. Studying mice whose orexin systems had been genetically destroyed – a state similar to humans suffering from narcolepsy, a neurological condition that causes unusual daytime sleepiness – Max B. Kelz, MD, PhD, an assistant professor in Penn’s Department of Anesthesiology and Critical Care and the Mahoney Institute of Neurological Sciences, found that these mice took much longer to emerge from general anesthesia than those with normal orexin signaling systems. However, the mice with faulty orexin systems did not appear to fall asleep faster during anesthesia, which suggests that different processes are at play when transitioning to and from the anesthetized stated.

“The modern expectation is that anesthesiologists can simply flip a consciousness switch as easily as we might turn the room lights on or off,” Kelz says. “However, what patients do not realize is that despite 160 years of widespread clinical use, the mechanisms through which the state of anesthesia arises and dissipates remain unknown.”

Kelz became interested in these questions after treating a narcoleptic patient who took more than six hours to regain consciousness after anesthesia, compared to the typical six minutes or so. By probing what’s different about the narcoleptic brain, the Penn study has established for the first time that the process of entry into and exit from the anesthetized state are not mirror images of one another.

Kelz and his colleagues, including Sigrid Veasey, MD, associate professor in the Department of Medicine’s Sleep Medicine division, hope that further research on the brain’s neural signaling systems will lead to novel ways to administer anesthesia and “jump start” a speedy, safe return to consciousness – particularly among patients who struggle to wake up or in patient groups that may be more prone to anesthesia side effects such as the elderly and patients with neurodegenerative disorders. The findings might also be used to create designer anesthetic agents that “hijack” the body’s natural sleep cycles to mimic a state closer to natural sleep than a chemically-induced coma, Kelz says.

Funding for this research was provided by the Foundation for Anesthesia Education and Research, the National Institues of Health, and the Department of Anesthesiology and Critical Care at the Penn School of Medicine.

Editor’s note: In addition to Penn researchers involved in the study, a narcoleptic patient who recently experienced a delayed emergence from anesthesia is also available for interviews.

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PENN Medicine is a $3.5 billion enterprise dedicated to the related missions of medical education, biomedical research, and excellence in patient care. PENN Medicine consists of the University of Pennsylvania School of Medicine (founded in 1765 as the nation's first medical school) and the University of Pennsylvania Health System.

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